Biomedical subjects

R Rosier

Publications and source records attributed to R Rosier.

6 recordsLinked to original sources

PubMed2001

PTHrP modulates chondrocyte differentiation through AP-1 and CREB signaling.

During the process of differentiation, chondrocytes integrate a complex array of signals from local or systemic factors like parathyroid hormone-related peptide (PTHrP), Indian hedgehog, bone morphogenetic proteins and transforming growth factor beta. While PTHrP is known to be a critical regulator of chondrocyte proliferation and differentiation, the signaling pathways through which this factor acts remain to be elucidated. Here we show that both cAMP response element-binding protein (CREB) and AP-1 activation are critical to PTHrP signaling in chondrocytes. PTHrP treatment leads to rapid CREB phosphorylation and activation, while CREB DNA binding activity is constitutive. In contrast, PTHrP induces AP-1 DNA binding activity through induction of c-Fos protein expression. PTHrP activates CRE and TRE reporter constructs primarily through PKA-mediated signaling events. Both signaling pathways were found to be important mediators of PTHrP effects on chondrocyte phenotype. Alone, PTHrP suppresses maturation and stimulates proliferation of the chondrocyte cultures. However, in the presence of dominant negative inhibitors of CREB and c-Fos, these PTHrP effects were suppressed, and chondrocyte maturation was accelerated. Moreover, in combination, the effects of dominant negative c-Fos and CREB are synergistic, suggesting interaction between these signaling pathways during chondrocyte differentiation.

Cell Differentiation↗

PubMed1999

Enlargement of remaining patella after partial patellectomy in rabbits.

PURPOSE: The purpose was to study the radiographic patellar tendon calcification and evaluate the histology of the healing interface between the patellar tendon and the remaining patella after partial patellectomy. METHODS: We removed the distal one-third of the patella in 24 rabbits. Specimens were harvested at 8, 12, and 24 wk postoperatively (N = 8 each). RESULTS: Histological observation demonstrated that healing interfaces between the patellar tendon and patella were structurally connected by scar tissue. The radiographic patellar tendon calcification next to the healing interface was in fact trabecular bone outgrowth histologically, resulting in an enlargement of the remaining patellar in length from 0.93+/-0.28 mm at week 8, 1.26+/-0.33 mm at week 12, to 2.5+/-1.12 mm at week 24. Metaplasia of the scar tissue observed next to the healing interface of the remaining patellar articular cartilage and the outgrowth of trabecular bone from the remaining patella with healing over time may increase the articular surface of the remaining patella after partial patellectomy. CONCLUSIONS: The remaining patella might be enlarged in length after partial patellectomy because of trabecular bone outgrowth and metaplasia with healing over time. Its theoretical advantages are an increased patellofemoral contact area and a diminished patellofemoral contact pressure following surgery.

Animals↗

PubMed1992

Sarcoma therapy: functional outcome and relationship to treatment parameters.

PURPOSE: To systematically assess the functional outcome of patients treated with surgery and irradiation for extremity or truncal sarcomas, and to correlate this outcome with a detailed analysis of the radiation dose distribution and surgical technique. Conservative surgery and radiation therapy (RT) are known to provide excellent local control, but the relationship of technique to functional outcome requires further study. METHODS AND MATERIALS: Forty-one patients were treated for lower extremity (25 patients, 61%), upper extremity (8 patients, 19.5%), and truncal (8, 19.5%) sarcomas from 1983 to 1990. Most patients had malignant fibrous histiocytoma (15), liposarcoma (8), or aggressive fibromatosis (6). Age ranged from 13 to 85 years (median 54). All patients received RT and 39 (95%) had surgery. The mean total RT dose was 59 Gy (range 55.8-64.8 Gy). A protocol for functional assessment was devised and included a 4 point scale (0-3) for each of seven functional parameters (range of motion, fibrosis, edema, pain, skin changes, muscle strength, gait, or upper extremity performance). An aggregate score was obtained by adding the seven parameter scores and compared with both a patient and physician overall functional rating score (excellent, good, fair, poor). Based on this analysis, aggregate scores were defined as < or = 3 = excellent, < or = 8 = good, < or = 13 = fair, and > 13 = poor, with 21 as the worst possible score. The same orthopaedic surgeon and radiation oncologist independently examined and rated 22 patients. An additional 17 patients were evaluated by record review. The median time from completion of radiation therapy was 30.5 months (range 7-95 months). A computerized radiation therapy dosimetric analysis was performed on 34 patients. RESULTS: Local control was achieved in 39 patients (95%), including 6 with aggressive fibromatosis. The mean functional outcome score was 5.1 with a range of 0-16. 34 patients (83%) had good or excellent functional outcomes. The rating system demonstrated minimal interobserver variability. There was a positive relationship between volume irradiated to > or = 55 Gy and functional score, strength, fibrosis, and skin changes. Total dose independent of volume was significantly associated with skin changes. Increasing peak dose (hot spot dose) was associated with fibrosis and skin changes. More fibrosis developed as the volume of the peak dose increased. A portion of the joint was treated in 5/33 extremity patients and the entire joint in 24/33 (mean dose 55.8 Gy, range 45-65 Gy). Neither range of motion nor total functional score was correlated with joint dose. Edema and functional score were not related to either the volume or percent of limb spared (receiving < or = 40 Gy). The physician functional status ratings generally concurred with patient self-assessments. CONCLUSIONS: A system for functional assessment has been developed which is easily performed and provides detailed information about patient functional outcome. This system can be used to evaluate the morbidity of combined modality sarcoma therapy. Doses up to 65 Gy, even over joint spaces, are not associated with significant morbidity. Only a small volume treated to < or = 40 Gy is required to maintain good outcome. The most important parameter appears to be the volume treated to > or = 55 Gy.

Adolescent↗

PubMed1990

The use of postoperative irradiation for the prevention of heterotopic bone after total hip replacement with biologic fixation (porous coated) prosthesis: an animal model.

Radiation has been shown to be effective in the prevention of heterotopic bone. The exact etiology of heterotopic bone is unknown. Total Hip prosthetic devices that do not depend upon bone cement for fixation have become increasingly popular. The mechanism by which the bone forms around the prosthesis is similar to the process by which fractures heal which has been shown to be sensitive to irradiation. Using a rabbit model we have undertaken a study to investigate the effect of irradiation on the bony ingrowth on porous coated implants. Forty-five rabbits had porous coated implants surgically placed in the tibiae bilaterally. Each rabbit had one tibae randomly irradiated with 1,000 cGy in 5 fractions starting on the first post-operative day. Animals were sacrificed weekly starting 2 weeks post-operatively and the tibae were sent for pullout studies. The amount of force necessary to pullout the treated tibae was statistically less than the amount of force necessary to remove the untreated tibae at 2 weeks. From 3 weeks on there was no difference in the force necessary to remove the prosthesis from the untreated or treated tibae. Histologically, the untreated tibae showed bone formation while the treated tibae did not. Because of these results, it is suggested that the treatment of patients at risk for development of heterotopic bone be modified to only include the area between the femur and pelvis avoiding treatment of the prosthetic device.

Animals↗

PubMed1990

Randomized trial comparing single dose versus fractionated irradiation for prevention of heterotopic bone: a preliminary report.

Radiation therapy has been shown to prevent heterotopic bone formation in high risk patients undergoing total hip replacement. A number of doses have been used without a randomized trial comparing one dose regimen against another. A prospective randomized trial was undertaken comparing 10 Gy in 5 fractions versus 8 Gy in 1 fraction. Forty-seven patients have been randomized at the time of this evaluation with 37 patients eligible for analysis. The pre-operative, immediate post-operative and 2 month post-operative radiographs were graded. At the time of this analysis, 17 patients were randomized to the 8 Gy arm with 20 patients in the 10 Gy arm. Patients were treated with limited fields so as to only cover the area at risk for development of heterotopic bone to prevent adverse effects on biologic fixation of uncemented implants. When comparing the pre-operative, operative, and 2 month post-operative radiographs, only four patients (1 patient in the 8 Gy arm and 3 patients in the 10 Gy arm), had an increase in the score. No patient had an increase in score to a clinically significant level, usually grade 3 or 4. These preliminary results appear to show that 8 Gy in a single fraction can be as effective as 10 Gy in 5 fractions in preventing heterotopic bone in susceptible individuals. Further follow-up of the remaining patients may confirm this.

Female↗

PubMedDate not supplied

Bone pain.

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Bone Neoplasms↗